image: Age-dependent increase in expression of Rubicon, a negative regulator of autophagy, is a cause of age-dependent autophagic impairment and contributes to acceleration of aging in animals. view more
Credit: Osaka University
Osaka, Japan – Autophagy is an important biological recycling mechanism that is used to maintain homeostasis (balance or equilibrium) within all types of animal tissue. Many studies have attempted to understand the relationship between the reduction of autophagy and progression of aging in animals; however, none have provided a clear explanation, until now.
In 2009, a research team led by Tamotsu Yoshimori at Osaka University identified Rubicon as a protein factor that suppresses autophagy by controlling a specific step in this pathway. This time, the team found that Rubicon expression levels increased in an age-related manner in worm, fly, and mouse tissues, publishing their findings in Nature Communications.
Autophagy allows degradation of damaged cellular components and helps to avoid the onset of a variety of diseases related to cellular stress and dysfunction, including cancer, neurodegenerative diseases, and metabolic syndromes. Reduced autophagy has recently been linked to progression of aging in animals. While a variety of methods can increase autophagy in aged animals, thereby slowing the aging process, there has been no definite finding regarding the underlying cause of naturally reduced autophagy.
"Rubicon has been linked to inhibition of the autophagic process, and knockout of Rubicon in mice helped to mitigate autophagy-related liver diseases," says Yoshimori. "Therefore, we suspected that Rubicon may directly affect aging through its interaction with autophagy."
In the study, increased levels of Rubicon were found in tissues from multiple aged model organisms (worms, flies, and mice). When the researchers suppressed Rubicon expression, all model organisms demonstrated increased autophagy activity, which led to improvement of multiple age-related factors and slightly increased lifespan in worms and flies.
"Our analyses revealed that Rubicon suppression in model organisms led to reduction of age-associated motor decline, as well as reduction of fibrosis," says Shuhei Nakamura, lead author on the study. "Importantly, we found that Rubicon suppression enabled aged mice to resist attempts to induce Parkinson's disease."
The findings in this study suggest that, because elevated levels of Rubicon lead to reduced autophagy in aged animals, suppression of Rubicon may be critical in extending healthy lifespan in humans.
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The article, "Suppression of autophagic activity by Rubicon is a signature of aging," was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-019-08729-6.
About Osaka University
Osaka University was founded in 1931 as one of the seven imperial universities of Japan and now has expanded to one of Japan's leading comprehensive universities. The University has now embarked on open research revolution from a position as Japan's most innovative university and among the most innovative institutions in the world according to Reuters 2015 Top 100 Innovative Universities and the Nature Index Innovation 2017. The university's ability to innovate from the stage of fundamental research through the creation of useful technology with economic impact stems from its broad disciplinary spectrum.
Website: https://resou.osaka-u.ac.jp/en/top
Journal
Nature Communications